Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press38510.17650/2313-805X-2021-8-4-8-20REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИEfficiency in different immunotherapy of cancer: literature reviewЭффективность иммунотерапии при разных злокачественных новообразованиях: обзор литературыhttps://orcid.org/0000-0003-1091-7528GaptulbarovaK. A.ГаптулбароваК. А.
Russian Federation

5 Kooperativny Ln., Tomsk 63400936 prospect Lenina, Tomsk 634050

634009 Томск, Кооперативный пер., 5634050 Томск, пр-т Ленина, 36

https://orcid.org/0000-0001-7419-4512TsyganovM. M.ЦыгановМ. М.
Russian Federation

Matvey Mikhailovich Tsyganov

5 Kooperativny Ln., Tomsk 634009

Матвей Михайлович Цыганов

634009 Томск, Кооперативный пер., 5

TsyganovMM@yandex.ruhttps://orcid.org/0000-0001-8815-2786IbragimovaM. K.ИбрагимоваМ. К.
Russian Federation

5 Kooperativny Ln., Tomsk 63400936 prospect Lenina, Tomsk 634050

634009 Томск, Кооперативный пер., 5634050 Томск, пр-т Ленина, 36

https://orcid.org/0000-0002-9657-9058PevznerA. M.ПевзнерА. М.
Russian Federation

5 Kooperativny Ln., Tomsk 63400936 prospect Lenina, Tomsk 634050

634009 Томск, Кооперативный пер., 5634050 Томск, пр-т Ленина, 36

https://orcid.org/0000-0002-5269-736XSpirinaL. V.СпиринаЛ. В.
Russian Federation

5 Kooperativny Ln., Tomsk 634009

634009 Томск, Кооперативный пер., 5

https://orcid.org/0000-0002-0714-8927LitviakovN. V.ЛитвяковН. В.
Russian Federation

5 Kooperativny Ln., Tomsk 634009

634009 Томск, Кооперативный пер., 5

Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesНаучно-исследовательский институт онкологии ФГБНУ «Томский национальный исследовательский медицинский центр» Российской академии наукNational Research Tomsk State UniversityФГАОУ ВО «Национальный исследовательский Томский государственный университет»15122021848201712202117122021Copyright ©; 2021, Gaptulbarova K.A., Tsyganov M.M., Ibragimova M.K., Pevzner A.M., Spirina L.V., Litviakov N.V.Copyright ©; 2021, Гаптулбарова К.А., Цыганов М.М., Ибрагимова М.К., Певзнер А.М., Спирина Л.В., Литвяков Н.В.2021Gaptulbarova K.A., Tsyganov M.M., Ibragimova M.K., Pevzner A.M., Spirina L.V., Litviakov N.V.Гаптулбарова К.А., Цыганов М.М., Ибрагимова М.К., Певзнер А.М., Спирина Л.В., Литвяков Н.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/385

It is known that the immune system plays one of the main roles in the development of oncology. This is confirmed by the fact that patients with congenital or acquired immunodeficiency have a higher risk of developing cancer. To date, there are several types of immunotherapy, each of which has its own mechanism of action. This review presents data from clinical studies of the main treatment options using immunotherapy mechanisms, such as cellular immunotherapy, the use of antibodies and cytokines, and combination immunotherapy (using checkpoint inhibitors). These data indicate a positive trend of this method of treatment in patients with cancer.

Известно, что иммунная система играет одну из основных ролей в развитии онкологии. Это подтверждается и тем, что пациенты с врожденным или приобретенным иммунодефицитом имеют более высокие риски развития рака. На сегодняшний день выделяют несколько видов иммунотерапии, каждый из которых имеет свой механизм действия. В этом обзоре представлены данные клинических исследований основных вариантов лечения, в основе которых лежат механизмы иммунотерапии, такие как клеточная иммунотерапия, применение антител и цитокинов, комбинированная иммунотерапия (с использованием чекпойнт-ингибиторов). Приведенные сведения свидетельствуют о положительной тенденции этого способа лечения у больных с онкологическими заболеваниями.

immunotherapycellular immunotherapycytokinescheckpoint inhibitorsprognosistreatment efficacyиммунотерапияклеточная иммунотерапияцитокиныингибиторы контрольных точекпрогнозэффективность леченияOiseth S.J., Aziz M.S. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat 2017;3(10):250–61. DOI: 10.20517/23944722.2017.41.Busch W. Aus der Sitzung der medicinischen Section vom 13 November 1867. Berl Klin Wochenschr 1868;5:137.Fehleisen F. Ueber die Züchtung der Erysipelkokken auf künstlichem Nährboden und ihre Übertragbarkeit auf den Menschen. Dtsch Med Wochenschr. 1882;8(31):553–4.Coley W.B. II. Contribution to the knowledge of sarcoma. Annals of surgery 1891;14(3):199.Pron’ko D. Aiming at cancer targets. Science and innovation = Nauka i innovacii 2017;3(169):29–31. (In Russ.).Пронько Д. Прицел на раковые мишени. Наука и инновации 2017;3(169):29–31.Old L.J., Clarke D.A.,Benacerraf B. Effect of Bacillus Calmette-Guerin infection on transplanted tumours in the mouse. Nature 1959;184(4682):291–2. DOI: 10.1038/184291a0.Morales A., Eidinger D., Bruce A. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 1976;116(2):180–2. DOI: 10.1016/S0022-5347(17)58737-6.Dock G. The influence of complicating diseases upon leukaemia. The American J Med Sci (1827–1924) 1904;127(4):563.Kelly E., Russell S.J. History of oncolytic viruses: genesis to genetic engineering. Mol Ther 2007;15(4):651–9. DOI: 10.1038/sj.mt.6300108.Ring C.J. Cytolytic viruses as potential anticancer agents. J Gen Virol 2002;83(3):491–502. DOI: https://doi.org/10.1099/00221317-83-3-491.Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest 2015;125(9):3335–7. DOI: 10.1172/JCI83871.Korneev K.V., Atretkhany K.-S.N., Drutskaya M.S. et al. TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. Cytokine 2017;89(1):127–35. DOI: 10.1016/j.cyto.2016.01.021.Kranz L.M., Diken M., Haas H., et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 2016;534(7607):396–401. DOI: 10.1038/nature18300.Riddell S.R. Progress in cancer vaccines by enhanced self-presentation. Procof Natl Acad Sci USA 2001;98(16):8933–5. DOI: 10.1073/pnas.171326398.Kroemer G., Galluzzi L., Kepp O., Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013;31(1):51–72. DOI: 10.1146/annurev-immunol-032712-100008.Apetoh L., Ghiringhelli F., Tesniere A. et al. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev2007;220(1):47–59. DOI: 10.1111/j.1600-065X.2007.00573.x.Tabi Z., Spary L.K., Coleman S. et al. Resistance of CD45RA− T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T Cells during radiation therapy of prostate cancer. J Immunol 2010;185(2):1330–9. DOI: 10.4049/jimmunol.1000488.Hirayama M., Nishimura Y. The present status and future prospects of peptide-based cancer vaccines. International immunology 2016;28(7):319–28. DOI: 10.1093/intimm/dxw027.Dastmalchi F., Karachi A., Mitchell D., Rahman M. Dendritic Cell therapy eLS 2018;1(1):1–27. DOI: 10.1002/9780470015902.a0024243.Jensen T.I., Axelgaard E., Bak R.O. Therapeutic gene editing in haematological disorders with CRISPR/Cas9. British J Haematol 2019;185(5):821–35. DOI: 10.1111/bjh.15851.Kiselevskij M.V., Chikileva I.O., Sitdikova S.M. et al. Prospects for the use of genetically modified lymphocytes with a chimeric T-cell receptor (CART cells) for the therapy of solid tumors. Immunologija = Immunology 2019;40(4):48–55. (In Russ.). DOI: 10.24411/0206-4952-2019-14006.Киселевский М.В., Чикилева И.О., Ситдикова С.М. и др. Перспективы применения генетически модифицированных лимфоцитов с химерным Т-клеточным рецептором (CAR-T-клеток) для терапии солидных опухолей. Иммунология 2019;40(4):48–55. DOI: 10.24411/0206-4952-2019-14006.Schultz L., Mackall C. Driving CAR T cell translation forward. Sci Transl Med 2019;11(481):eaaw2127. DOI: 10.1126/scitranslmed.aaw2127.Maus M.V., Haas A.R., Beatty G.L. et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 2013;1(1):26–31. DOI: 10.1158/2326-6066.CIR-13-0006.Ryman J.T., Meibohm B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol 2017;6(9):576–88. DOI: 10.1002/psp4.12224.Scott A.M., Wolchok J.D., Old L.J. Antibody therapy of cancer. Nat Rev Cancer 2012;12(4):278–87. DOI: 10.1038/nrc3236.Weiner L.M., Surana R., Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 2010;10(5):317–27. DOI: 10.1038/nri2744.Seidel U.J.E., Schlegel P., Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Frontiers in immunology 2013;4(76):1–8. DOI: 10.3389/fimmu.2013.00076.Lee S., Margolin K., Cytokines in cancer immunotherapy. Cancers 2011;3(4):3856–93. DOI: 10.3390/cancers3043856.Goldstein D., Laszlo J. The role of interferon in cancer therapy: a current perspective. CA Cancer J Clin 1988;38(5):258–77. DOI: 10.3322/canjclin.38.5.258.Nicholas C., Lesinski G.B. Immunomodulatory cytokines as therapeutic agents for melanoma. Immunotherapy 2011;3(5):673–90. DOI: 10.2217/imt.11.45.Ardolino M., Hsu J., Raulet D.H. Cytokine treatment in cancer immunotherapy. Oncotarget 2015;6(23):19346–7. DOI: 10.18632/oncotarget.5095.Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 2004;4(1):11–22. DOI: 10.1038/nrc1252.Dunn G.P., Koebel C.M., Schreiber R.D. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 2006;6(11):836–48. DOI: 10.1038/nri1961.Coventry B.J., Ashdown M.L. The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses. Cancer Manag Res 2012;4(1):215–21. DOI: 10.2147/CMAR.S33979.Constantinescu S.N., Croze E., Wang C. et al. Role of interferon alpha/beta receptor chain 1 in the structure and transmembrane signaling of the interferon alpha/beta receptor complex. Proceedings of the Nat Acad Sci 1994;91(20):9602–6. DOI: 10.1073/pnas.91.20.9602.Katze M., He Y., Gale M. Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2002;2(1):675–87. DOI: 10.1038/nri888.Müller L., Aigner P., Stoiber D. Type I interferons and natural killer cell regulation in cancer. Front Immunol 2017;8(304):1– 11. DOI: 10.3389/fimmu.2017.00304. eCollection 2017.Trepiakas R., Pedersen A.E., Met Ö., Svane I.M. Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function. Vaccine 2009;27(16):2213–9. DOI: 10.1016/j.vaccine.2009.02.015.Siegal F.P., Kadowaki N., Shodell M. et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999;284(5421):1835–7. DOI: 10.1126/science.284.5421.1835.Tarhini A.A., Cherian J., Moschos S.J. et al. Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J Clin Oncol 2012;30(3):322–8. DOI: 10.1200/JCO.2011.37.5394.Zeestraten E.C., Speetjens F.M., Welters M.J. et al. Addition of interferon α to the p53 SLP vaccine results in increased production of interferon γ in vaccinated colorectal cancer patients: a phase I/II clinical trial. Int J Cancer 2013;132(7):1581–91. DOI: 10.1002/ijc.27819.Wang X., Rickert M., Garcia K.C. Structure of the quaternary complex of Interleukin-2 with Its α, β, and γ receptors. Science 2005;310(5751):1159–63. DOI: 10.1126/science.1117893.Boyman O., Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012;12(3):180–90. DOI: 10.1038/nri3156.Waldmann T.A. Cytokines in cancer immunotherapy. Cold Spring Harb Perspect Biol 2018;10(12):a028472. DOI: 10.1101/cshperspect.a028472.Lazer D., Pentland A.S., Adamic L. et al. Life in the network: the coming age of computational social science. Science 2009;323(5915):721–3. DOI: 10.1126/science.1167742.Chen D.S., Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity 2013;39(1):1–10. DOI: 10.1016/j.immuni.2013.07.012.Ott P.A., Hodi F.S., Kaufman H.L. et al. Combination immunotherapy: a road map. J Immunother Cancer 2017;5(1):1–15. DOI: 10.1186/s40425-017-0218-5.Krummel M.F., Allison J.P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182(2):459–65. DOI: 10.1084/jem.182.2.459.Wilky B.A., Immune checkpoint inhibitors: the linchpins of modern immunotherapy. Immunol Rev 2019;290(1):6–23. DOI: 10.1111/imr.12766.Schneider H., Smith X., Liu H. et al. CTLA-4 disrupts ZAP70 microcluster formation with reduced T cell/APC dwell times and calcium mobilization. Eur J Immunol 2008;38(1):40–7. DOI: 10.1002/eji.200737423.Kubsch S., Graulich E., Knop J., Steinbrink K. Suppressor activity of anergic T cells induced by IL-10-treated human dendritic cells: association with IL-2and CTLA-4-dependent G1 arrest of the cell cycle regulated by p27Kip1. Eur J Immunol 2003;33(7):198897. DOI: 10.1002/eji.200323600.Olsson C., Riebeck K., Dohlsten M., Michaëlsson E. CTLA-4 ligation suppresses CD28-induced NF-κB and AP-1 activity in mouse T cell blasts. J Biol Chem 1999;274(20):14400–5. DOI: 10.1074/jbc.274.20.14400.Ishida Y., Agata Y., Shibahara K., Honjo T., Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11(11):3887–95. DOI: 10.1002/j.1460-2075.1992.tb05481.x.Okazaki T., Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 2007;19(7):813–24. DOI: 10.1093/intimm/dxm057.Riella L.V., Paterson A.M., Sharpe A.H., Chandraker A. Role of the PD-1 Pathway in the Immune Response. Am J Transplant 2012;12(10):2575–87. DOI: 10.1111/j.1600-6143.2012.04224.x.Park J.J., Omiya R., Matsumura Y. et al. B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood 2010;116(8):1291–8. DOI: 10.1182/blood-2010-01-265975.Topalian S.L., Hodi F.S., Brahmer J.R. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New Engl J Med 2012;366(26):2443–54. DOI: 10.1056/NEJMoa1200690.Sharma P., Retz M., Siefker-Radtke A. et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, singlearm, phase 2 trial. Lancet Oncol 2017;18(3):312–22. DOI: 10.1016/S14702045(17)30065-7.Motzer R.J., Tannir N.M., McDermott D.F. et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med2018;378(14):1277–90. DOI: 10.1056/NEJMoa1712126.Patnaik A., Kang S.P., Rasco D. et al. Phase I study of pembrolizumab (MK3475; anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res 2015;21(19):4286–93. DOI: 10.1158/1078-0432.CCR-14-2607.Motzer R.J., Penkov K., Haanen J. et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380(12):1103–15. DOI: 10.1056/NEJMoa1816047.Brahmer J.R., Tykodi S.S., Chow L.Q. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366(26):2455–65. DOI: 10.1056/NEJMoa1200694.Powles T., O’Donnell P.H., Massard C. et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study. JAMA Oncol 2017;3(9):1–10. DOI: 10.1001/jamaoncol.2017.2411.Schmid P., Cruz C., Braiteh F.S. et al. Atezolizumab in metastatic TNBC (mTNBC): long-term clinical outcomes and biomarker analyses. AACR 2017;77(13):1. DOI: 10.1158/1538-7445.AM2017-2986.Postow M.A., Chesney J., Pavlick A.C. et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015;372(21):2006–17. DOI: 10.1056/NEJMoa1414428.Pfirschke C., Engblom C., Rickelt S., Cortez-Retamozo V. et al., Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity 2016;44(2):343–54. DOI: 10.1016/j.immuni.2015.11.024.Fyfe G., Fisher R.I., Rosenberg S.A. et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995;13(3):688–96. DOI: 10.1200/JCO.1995.13.3.688.Rosenberg S.A., Yang J.C., White D.E., Steinberg S.M. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg 1998;228(3):307–19. DOI: 10.1097/00000658-199809000-00004.Merchant R.E., Grant A.J., Merchant L.H., Young H.F. Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer 1988;62(4):665–71. DOI: 10.1002/1097-0142(19880815)62:4<665::AID-CNCR2820620403>3.0.CO;2-O.Atkins M.B., Lotze M.T., Dutcher J.P. et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17(7):2105. DOI: 10.1200/JCO.1999.17.7.2105.Toh U., Yamana H., Sueyoshi S. et al. Locoregional cellular immunotherapy for patients with advanced esophageal cancer. Clin Cancer Res 2000;6(12):4663–73.Nishiyama T., Tachibana M., Horiguchi Y. et al. Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24specific MAGE-3 peptide. Clin Cancer Res 2001;7(1):23–31.Kabbinavar F., Hurwitz H.I., Fehrenbacher L. et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21(1):60–5. DOI: 10.1200/JCO.2003.10.066.Hurwitz H., Fehrenbacher L., Novotny W. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335–42. DOI: 10.1056/NEJMoa032691.Davis I.D., Skrumsager B.K., Cebon J. et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin Cancer Res 2007;13(12):3630–6. DOI: 10.1158/1078-0432.CCR-07-0410.Giantonio B.J., Catalano P.J., Meropol N.J. et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007;25(12):1539–44. DOI: 10.1200/JCO.2006.09.6305.Iqbal S., Goldman B., Lenz H. et al. S0413: a phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer. J Clin Oncol 2007;25(18_suppl):4621. DOI: 10.1200/jco.2007.25.18_suppl.4621.Hecht J.R., Mitchell E., Chidiac T. et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009;27(5):672–80. DOI: 10.1200/JCO.2008.19.8135.Petrella T.M., Tozer R., Belanger K. et al. Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol 2012;30(27):3396–401. DOI: 10.1200/JCO.2011.40.0655.Gettinger S., Rizvi N.A., Chow L.Q. et al. Nivolumab monotherapy for first-line treatment of advanced non small-cell lung cancer. J Clin Oncol 2016;34(25):2980–7. DOI: 10.1200/JCO.2016.66.9929.Eggermont A.M., Chiarion-Sileni V., Grob J.J. et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 2016;375(19):1845–55. DOI: 10.1056/NEJMoa1611299.Davar D., Ding F., Saul M. et al. Highdose interleukin-2 (HD IL-2) for advanced melanoma: a single center experience from the University of Pittsburgh Cancer Institute. J Immunother Cancer 2017;5(74):1–10. DOI: 10.1186/s40425017-0279-5.Kok M., Horlings H., van de Vijver K. et al. LBA14Adaptive phase II randomized non-comparative trial of nivolumab after induction treatment in triple negative breast cancer: TONIC-trial. Ann Oncol 2017;28(suppl_5):1.Hammers H.J., Plimack E.R., Infante J.R. et al. Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: the CheckMate 016 study. J Clin Oncol 2017;35(34):3851–8. DOI: 10.1200/JCO.2016.72.1985.Abakushina E.V., Pasova I.A., Pochuev T.P. et al. Adoptive immunotherapy with activated lymphocytes in the complex therapy of patients with gastrointestinal cancer. Rossijskij bioterapevticheskij zhurnal = Russian Biotherapeutic Journal 2017;16(S1):3. (In Russ.).Абакушина Е.В., Пасова И.А., Почуев Т.П. и др. Адоптивная иммунотерапия активированными лимфоцитами в комплексной терапии пациентов с раком желудочно-кишечного тракта. Российский биотерапевтический журнал 2017;16(S1):3.Escudier B., Motzer R.J., Sharma P. et al. Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. Eur Urol 2017;72(3):368–76. DOI: 10.1016/j.eururo.2017.03.037.Weber J., Mandala M., Del Vecchio M. et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017;77(19):1824–35. DOI: 10.1056/NEJMoa1709030.Adams S., Loi S., Toppmeyer D.L. et al. KEYNOTE-086 cohort B: Pembrolizumab monotherapy for PD-L1–positive, previously untreated, metastatic triplenegative breast cancer (mTNBC). AACR 2018;78(4):1. DOI: 10.1158/1538-7445.SABCS17-PD6-10.Buchbinder E.I., Dutcher J.P., Daniels G.A. et al. Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition. J Immunother Cancer 2019;7(1):1–7. DOI: 10.1186/s40425-019-0522-3.Koster B.D., Santegoets S.J., Harting J. et al. Correction to: Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial. Cancer Immunol Immunotherap 2019;68(6):1037. DOI: 10.1007/s00262-019-02328-6.Topalian S.L., Hodi F.S., Brahmer J.R. et al. Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab. JAMA Oncol 2019;5(10):1411–20. DOI: 10.1001/jamaoncol.2019.2187.Borobova E.A., Zheravin A.A. Natural killers in immunotherapy of oncological diseases. Sibirskij onkologicheskij zhurnal = Siberian Journal of Oncology 2018;17(6):97–103. (In Russ.). DOI: 10.21294/1814-48612018-17-6-97-104.Боробова Е.А., Жеравин А.А. Натуральные киллеры в иммунотерапии онкологических заболеваний. Сибирский онкологический журнал 2018;17(6):97–103. DOI: 10.21294/1814-48612018-17-6-97-104.Davila M.L., Riviere I., Wang X. et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Medi 2014;6(224):224–5. DOI: 10.1126/scitranslmed.3008226.Xu Y., Zhang M., Ramos C.A. et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR. CD19-T cells and are preserved by IL-7 and IL-15. Blood 2014;123(24):3750–9. DOI: 10.1182/blood-2014-01-552174.